Acta Neurochirurgica

, Volume 138, Issue 10, pp 1230–1240 | Cite as

Development of calcitonin gene-related peptide slow-release tablet implanted in CSF space for prevention of cerebral vasospasm after experimental subarachnoid haemorrhage

  • I. Ahmad
  • S. Imaizumi
  • H. Shimizu
  • T. Kaminuma
  • N. Ochiai
  • M. Tajima
  • T. Yoshimoto
Experimental Research

Summary

The calcitonin gene-related peptide (CGRP), a known potent intrinsic cerebral vasodilator, is contained in the sensory nerves from trigeminal ganglia that inervate the cerebral arteries. We previously reported that human α CGRP (hCGRP) dilates spastic cerebral arteries after experimental subarachnoid haemorrhage (SAH) in rabbits. In the present study, we investigated the prophylactic potential of a sustained higher cerebrospinal fluid level ofhCGRP against experimental cerebral vasospasm. AnhCGRP slow-release tablet (hCGRP s-r tablet) was developed for cisternal implantation. Experimental SAH was induced by percutaneous cisternal injection of autologous arterial blood. Angiography was initiated on day 1 (before SAH) and performed everyday. ThehCGRP s-r tablet was implanted into the cisterna magna on day 2 in the treated groups. The spastic response of the basilar artery was maximized on day 4 in the non-treated (80.7% of day 1) and the placebo-treated (79.3%) groups. In contrast, the arterial diameters on day 4 were 96.1% and 90.5% of day 1 in the groups implanted withhCGRP 24 μg and 153 μg s-r tablets, respectively. We also measured the concentration ofhCGRP in the cerebrospinal fluid (CSF) following implantation of thehCGRP 24 μg s-r tablet in the cisterna magna. The hCGRP concentration before implantation was below the dectable level. Following implantation, thehCGRP level in the CSF was 23.12 nmol/L on the second day and remained at elevated levels until the fifth day. These experiments suggest that the intrathecal single implantation of thehCGRP s-r tablet could produce an elevated concentration ofhCGRP in the CSF over five days and have prevented the cerebral vasospasm after SAH in the rabbit. ThehCGRP s-r tablet may be clinically applicable in the treatment of patients with SAH against cerebral vasospasm.

Keywords

Calcitonin gene-related peptide slow-release tablet subarachnoid haemorrhage cerebral vasospasm 

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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • I. Ahmad
    • 1
  • S. Imaizumi
    • 2
  • H. Shimizu
    • 1
  • T. Kaminuma
    • 3
  • N. Ochiai
    • 3
  • M. Tajima
    • 3
  • T. Yoshimoto
    • 1
  1. 1.Department of NeurosurgeryTohoku University School of MedicineSendai
  2. 2.Department of NeurosurgeryIwate Prefectoral Isawa HospitalIwate
  3. 3.Shiseido Research CentreYokohamaJapan

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